LCH-CLO: Clofarabine for Langerhans Cell Histiocytosis and LCH-related disorders

Phase II Study of Clofarabine in Patients with Recurrent or Refractory Langerhans Cell Histiocytosis and LCH-Related Disorders

Category:

Histiocytic Disorders

Diseases Treated:

Langerhans cell histiocytosis and LCH-related disorders

Eligibility Overview:

  • Prior diagnosis of Langerhans cell histiocytosis or LCH-related disorder
  • Evidence of active disease
  • Performance Score > 70% (use Lansky score for age < 16 and Karnofsky score for age ≥16)
  • Any age
  • Adequate organ functions
  1. Brief Summary

    Langerhans cell histiocytosis (LCH) is a rare disorder caused by clonal proliferation of Langerhans cells that is characterized by a spectrum of varying degrees of organ involvement and dysfunction. Mortality rates for patients with organ dysfunction may reach 30 to 40 percent. For patients with low-risk disease, while cure is almost universal, disease reactivation rates exceed 30 percent.

    LCH-related disorders include Juvenile Xanthogranuloma (JXG), Rosai Dorfman Disease (RDD), Erdheim Chester Disease (ECD), Histiocytic Sarcoma (HS), and Interdigitating Dendritic cell Sarcoma/Histiocytosis (IDCMH).  There is currently no established therapy for any of these entities. Thus, new treatments are needed.

    Clofarabine is a rationally designed, second generation purine nucleoside analogue that has proven to be effective in patients with refractory LCH and LCH-related disorders. This Phase II study will evaluate the efficacy of clofarabine in participants with multi-focal or low-risk multi-system LCH in whom disease has recurred (Stratum A) and in high-risk participants with recurrent or refractory multisystem LCH with risk-organ involvement (Stratum B). Additionally, in Stratum C, the study will register participants with histiocytic diseases other than LCH who require systemic therapy to accumulate experience with clofarabine in this rare patient population.

    Primary Objective

    • To estimate the response rate of participants with recurrent LCH to clofarabine within each of two strata: a) low-risk participants with disease reactivation; and, b) high-risk participants with risk-organ involvement that is refractory to standard treatment.

    Eligibility Criteria

    Inclusion criteria include:

    • Prior diagnosis of Langerhans cell histiocytosis (Stratum A and Stratum B) or LCH-related disorder (Stratum C)
    • Evidence of active disease
    • Performance Score > 70% (use Lansky score for age < 16 and Karnofsky score for age = >16
    • Any age
    • Strata requirements:
      • Stratum A (Low-risk): Failed at least one prior systemic chemotherapy regimen
      • Stratum B (High-risk): Failed at least one prior systemic chemotherapy regimen, which must include cladribine/cytarabine, or is not considered to be eligible for such treatment
      • Stratum C (LCH-related disorders):
        • LCH-related disorders which require systemic chemotherapy
        • Rosai Dorfman Disease (RDD) patients must have failed treatment with corticosteroid
        • Erdheim Chester Disease (ECD) patients with confirmed BRAF V600E mutation must have failed treatment with a BRAF inhibitor, or are not considered to be eligible for such treatment
    • Adequate bone marrow functions, except those with involvement of hematopoietic system, for whom criteria may be waived
    • Absolute neutrophil count > 750 cells/µL
    • Platelets > 75,000 cells/µL
    • Adequate organ functions
    • Negative pregnancy test within 14 days prior to enrollment (females)\

    Exclusion Criteria include:

    • Chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to enrollment
    • Receiving other investigational agents targeting histiocytosis
    • History of prior hematopoietic stem cell transplantation; elevated conjugated serum bilirubin at study entry; uncontrolled systemic fungal, bacterial or other infection’ history of hepatitis B or cirrhosis
    • HIV-positive on combination antiretroviral therapy

    Study Sites

    St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.

  2. About this study

    This clinical trial will test an investigational drug treatment for Langerhans cell histiocytosis, a rare disorder also known as LCH. Investigational means the drug is still being studied. Study participants will receive a drug called clofarabine. This drug is a chemotherapy medicine that has been used and approved by the U.S. Food and Drug Administration (FDA) to treat leukemia in children and adults. Other studies suggest the drug may also be effective in patients with LCH and other histiocytic disorders.

    Purpose of this clinical trial

    The main goal of this study is to see how well clofarabine treats LCH that has come back after treatment (recurrent) or has not responded to treatment (refractory).

    Eligibility overview

    • Prior diagnosis of Langerhans cell histiocytosis or LCH-related disorder
    • Evidence of active disease
    • Performance Score > 70% (use Lansky score for age < 16 and Karnofsky score for age ≥ 16
    • Any age
    • Adequate organ functions
  3. LCH-CLO  Quick View
    Sponsor North American Consortium for Histiocytosis
    Clinicaltrials.gov identifier NCT02425904
    Trial start date May 2015            
    Estimated enrollment 85 (6 at St. Jude)
    Study type Interventional
    Study phase Phase II
    Conditions Langerhans cell histiocytosis and LCH-related disorders
    Ages All
    Principal investigator Patrick Campbell, MD, PhD (at St. Jude)
    Study sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss LCH-CLO
    St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org
     

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.